Metabolic Bone Disease in Very Low-Birth-Weight Neonates

Document Type : Original Article

Authors

1 Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran

2 2. Department of Nursing, Faculty of Nursing & Midwifery, Najafabad Branch, Islamic Azad University, Najafabad, Isfahan, Iran

3 Kashan University of Medical Sciences, Kashan, Iran

4 Department of Radiology, Kashan University of Medical Sciences, Kashan, Iran

5 Department of Biostatistics and Public Health, Kashan University of Medical Sciences, Kashan, Iran

Abstract

Background: Metabolic bone diseases (MBD), including rickets and osteopenia, are important neonatal complications among preterm infants. This study aimed to determine the prevalence and risk factors of MBD in neonates with very low birth weight (VLBW).
Methods: This prospective study was conducted on VLBW infants from January 2012 to July 2013. Inclusion criteria were birth weight of ≤1500 g and age of ≤7 days, and the exclusion criteria were cholestatic disorders, skeletal anomalies and genetic syndromes. Serum calcium, phosphorus and alkaline phosphatase (ALP) concentrations were measured regularly until the 12th week of birth. In addition, wrist and chest radiographs were obtained from the neonates at 8-12 weeks of age.
Results: In total, 58 neonates with the mean gestational age of 30.6±2.65 weeks, weight of 1265±262 g and height of 38.06±2.49 cm were enrolled in this study. The correlation between biochemical parameters in multiple analysis and radiological findings of rickets was examined, and a significant association was observed between serum phosphorus level at the first week of age and the incidence of rickets. Moreover, 14 infants had only one radiologic sign of rickets (e.g. fraying, cupping, widening or lack of provisional zone of calcification (PZC), and 8 subjects (13.7%) showed at least two radiologic signs. The prevalence of osteopenia and rickets among infants with birth weight of <1200 g was 32.7% and 81.8%, respectively. In addition, 72.2% of the neonates with birth weight of >1200 g had normal X-rays (P=0.036).
Conclusion: Despite the remarkable advances in the management of VLBW infants, MBD is still a prevalent complication during the neonatal period. According to the results of this study, birth weight and gestational age are the most significant risk factors for MBD.

Keywords


1.   Lothe A, Sinn J, Stone M. Metabolic bone disease of prematurity and secondary hyperparathyroidism. J Paediatr Child Health. 2011; 47:550-3.
2.   Pieltain C, de Halleux V, Senterre T, Rigo J. Prematurity and bone health. World Rev Nutr Diet. 2013; 106:181-8.
3.   Sharma M, Sohi I. Linear and skull growth in extremely low birth weight babies with rickets of prematurity. Indian J Pediatr. 2012; 79:655-8.
4.   Chen HY, Chiu LC, Yek YL, Chen YL. Detecting rickets in premature infants and treating them with calcitriol: experience from two cases. Kaohsiung J Med Sci. 2012; 28:452-6.
5.   Greenbaum LA. Rickets and Hypervitaminosis D.. Kliegman RM, editor. 19th ed. Philadelphia: ELSEVIER; 2011. P:208 .
6.   Tomlinson C, McDevitt H, Ahmed SF, White MP. Longitudinal changes in bone health as assessed by the speed of sound in very low birth weight preterm infants. J Pediatr. 2006; 148:450-5.
7.   Rustico SE, Calabria AC, Garber SJ. Metabolic bone disease of prematurity.Journal of Clinical & Translational Endocrinology. 2014; 1:85-91.
8.   Grataroli E. Newborn Ostheopenia; 2014. Available from: http://flipper.diff.org/app/items/6486.
9.   Mihatsch W, Trotter A, Pohlandt F. Calcium and phosphor intake in preterm infants: sensitivity and specifity of 6-hour urine samples to detect deficiency. Klin Padiatr. 2012; 224:61-5.
10. Pereira-da-Silva L, Costa A, Pereira L, Filipe A, Virella D, Leal E, et al. Early high calcium and phosphorus intake by parenteral nutrition prevents short-term bone strength decline in preterm infants. J Pediatr Gastroenterol Nutr. 2011; 52:203-9.
11. Wesol-Kucharska D, Laskowska J, Sibilska M, Friedman-Gruszczynska J, Blonska M, Gawecka A, et al. [Prevention of osteopenia in premature infants]. Med Wieku Rozwo. 2008; 12:924-32.
12. Siddhartha S, Sharma S, Arya S, Chellani H, Roy N. Metabolic bone disease in low birth weight babies between 1500 and 2000 g on exclusive breast feeding. Astrocyte. 2014; 1:75-9.
13. Maas C, Pohlandt F, Mihatsch WA, Franz AR. [Prevention of bone mineral deficiency in premature infants: review of the literature with focus on monitoring of urinary calcium and phosphate]. Klin Padiatr. 2012; 224:80-7.
14. Viswanathan S, Khasawneh W, McNelis K, Dykstra C, Amstadt R, Super DM, et al. Metabolic bone disease: a continued challenge in extremely low birth weight infants. JPEN J Parenter Enteral Nutr. 2013; 38:982-90. 
15. Agarwal R, Virmani D, Jaipal ML, Gupta S, Gupta N, Sankar MJ, et al. Vitamin D status of low birth weight infants in Delhi: a comparative study. J Trop Pediatr. 2012; 58:446-50.
16. Mitchell SM, Rogers SP, Hicks PD, Hawthorne KM, Parker BR, Abrams SA. High frequencies of elevated alkaline phosphatase activity and rickets exist in extremely low birth weight infants despite current nutritional support. BMC pediatr. 2009; 9:47.
17. Dokos C, Tsakalidis C, Tragiannidis A, Rallis D. Inside the “fragile” infant: pathophysiology, molecular background, risk factors and investigation of neonatal osteopenia. Clin Cases Miner Bone Metab. 2013; 10(2):86-90.
18. Lee SM, Namgung R, Park MS, Eun HS, Park KI, Lee C. High incidence of rickets in extremely low birth weight infants with severe parenteral nutrition-associated cholestasis and bronchopulmonary dysplasia. J Korean Med Sci. 2012; 27:1552-5.
19. Rennie LM, Beattie TF, Wilkinson AG, Crofton P, Bath LE. Incidental radiological diagnosis of rickets. Emerg Med J. 2005; 22:534-7.
20. Funke S, Morava E, Czako M, Vida G, Ertl T, Kosztolanyi G. Influence of genetic polymorphisms on bone disease of preterm infants. Pediatr Res. 2006; 60:607-12.
21. Rohana J, Hasmawati J, Zulkifli SZ. Risk factors associated with low bone mineral content in very low birth weight infants. Singapore Med J. 2007; 48:191-4.
22. Harrison CM, Johnson K, McKechnie E. Osteopenia of prematurity: a national survey and review of practice. Acta Paediatr. 2008; 97:407-13.
23. Chauhan SS, Sarkar PD, Bhimte B. Prematurity and related biochemical outcomes: study of bone mineralization and renal function parameters in preterm infants. Biochemistry Res Int. 2011; 2011.
 24.         Backstrom MC, Kouri T, Kuusela AL, Sievanen H, Koivisto AM, Ikonen RS, et al. Bone isoenzyme of serum alkaline phosphatase and serum inorganic phosphate in metabolic bone disease of prematurity. Acta Paediatr. 2000; 89:867-73.
25. Lapillonne A, Salle BL, Glorieux FH, Claris O. Bone mineralization and growth are enhanced in preterm infants fed an isocaloric, nutrient-enriched preterm formula through term. Am J Clin Nutr. 2004; 80:1595-603.
26. Boceanu E, Ilie C, Enatescu I, Iacob D. Metabolic bone disease of prematurity. Revista Societăţii Române de Chirurgie Pediatrică. 2013:42.
27. Torabi Z, Moemeni N, Ahmadiafshar A, Mazloomzadeh S. The effect of calcium and phosphorus supplemtation on metabolic bone disorders in premature infants. J Pak Med Assoc. 2014; 64:635-9.